Diabetes mellitus is a disease characterized by hyperglycemia, polyuria, and wasting. Hyperglycemia is due to decreased utilization of glucose and also increased production of glucose.
The discovery of insulin in 1922 has made it possible to control the blood glucose level in diabetic patients, at least partially. This enhanced the well being and survival of diabetic patients; however, recent studies indicate that long term complications of diabetes such as blindness, heart failure, kidney failure, neuropathy and vascular disease are not completely obviated by insulin therapy. It has been suggested that the foregoing long term complications are due to one or more of the following reasons: (1) the control of glucose levels by periodic injection of insulin is imperfect and better glucose control is important, (2) the control of metabolic substances other than glucose is important and necessary for the management of the diabetic patient, and (3) the levels of hormones other than insulin also should be adjusted, i.e., the glucagon concentration should be reduced.
To improve the control of glucose levels, several methods have been suggested. Among such methods are the "close control" method whereby a patient is hospitalized with attendant frequent assays of blood sugars and frequent insulin injections (e.g., before each meal). To effect control, the individual or the clinical laboratory has to perform frequent blood sugar analyses on a regular basis.
A further extension of the aforementioned treatment by "close control" is the use of a continuous or constant rate infusion of insulin using an insulin dispenser for infusion of this hormone into the patient. With such a machine, the rate of insulin administration must be predetermined by a physician, and further requires the maintenance of a steady diet and a continued uniform sensitivity of the patient to insulin.
It has been proposed to use a sensor responsive to the patient's glucose level for regulating the rate of insulin administration by the aforementioned insulin dispenser. However, all glucose sensors proposed to date have been unstable in vivo when used for time periods in excess of several weeks and thus are not very practical. A variety of problems have been encountered with such sensors: (1) Sensors that rely on the oxidation of glucose (with glucose oxidase) exhibit stability problems due to the inherent instability or inactivation of such enzymes, (2) sensors relying on the direct oxidation of glucose (by means of electrodes) encounter undesirable polarization phenomena on the electrode surfaces, (3) the in vivo period of reliability of heretofore known implanted glucose sensors is shortened by fibrous or fibrinous encasement. This is so because all heretofore known glucose sensors are rate-dependent. That is, the glucose concentration in a patient's blood is indicated by the reaction rate of glucose at the sensor. Glucose in the blood must diffuse to the electrode or to the enzyme present in the sensor. For reliable sensor signal output, a constant mass transfer resistance of glucose to the sensing element must be maintained. Progressive fibrous or fibrinous encasement of the sensing element continuously alters such resistance and requires frequent recalibration of the sensor.
Accordingly, there exists a pressing need for a reliable means for administering insulin to a diabetic patient utilizing a stable implantable sensor.